Premium
Late‐onset Pompe disease in France: molecular features and epidemiology from a nationwide study
Author(s) -
Semplicini Claudio,
Letard Pascaline,
De Antonio Marie,
Taouagh Nadjib,
Perniconi Barbara,
Bouhour Françoise,
EchanizLaguna Andoni,
Orlikowski David,
Sacconi Sabrina,
SalortCampana Emmanuelle,
Solé Guilhem,
Zagnoli Fabien,
Hamroun Dalil,
Froissart Roseline,
Caillaud Catherine,
Laforêt Pascal
Publication year - 2018
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-018-0243-7
Subject(s) - missense mutation , frameshift mutation , nonsense mutation , age of onset , genotype , epidemiology , medicine , genetics , mutation , pediatrics , newborn screening , genotype phenotype distinction , exon , fabry disease , compound heterozygosity , disease , biology , gene
Pompe disease (PD) is caused by a deficiency of lysosomal acid α‐glucosidase resulting from mutations in the GAA gene. The clinical spectrum ranges from a rapidly fatal multisystemic disorder (classic PD, onset < 1 year) to a milder adult onset myopathy. The aims of this study were to characterize the GAA mutations, to establish the disease epidemiology, and to identify potential genotype‐phenotype correlations in French late‐onset PD patients (onset ≥ 2 years) diagnosed since the 1970s. Data were collected from the two main laboratories involved in PD diagnosis and from the French Pompe registry. Two hundred forty‐six patients (130 females and 116 males) were included, with a mean age at diagnosis of 43 years. Eighty‐three different mutations were identified in the GAA gene, among which 28 were novel. These variants were spread all over the sequence and included 42 missense (one affecting start codon), 8 nonsense, 15 frameshift, 14 splice mutations, 3 small in‐frame deletions, and one large deletion. The common c.‐32‐13T>G mutation was detected in 151/170 index cases. Other frequent mutations included the exon 18 deletion, the c.525del, and the missense mutations c.1927G>A (p.Gly643Arg) and c.655G>A (p.Gly219Arg). Patients carrying the c.‐32‐13T>G mutation had an older mean age at onset than patients non‐exhibiting this mutation (36 versus 25 years). Patients with the same genotype had a highly variable age at onset. We estimated the frequency of late‐onset PD in France around 1/69,927 newborns. In conclusion, we characterized the French cohort of late‐onset PD patients through a nationwide study covering more than 40 years.